This project addresses the effect of point mutations on the structure of hemoglobin S fibers and fiber networks. The proposed elements have three principal foci: (1) the interactions between fibers which are responsible for heterogenous nucleation and fiber cross-linking; (2) the effect of components of the red cell on these fundamental processes and (3) the detailed characterization of the kinetics of fiber and gel melting. Differential interference contrast (DIC) light microscopy, pioneered by Dr. Briehl, will also be used to examine the polymerization and depolymerization of mutant hemoglobins. Photolysis of carbon monoxide will be used as the primary technique to prepare polymerizing samples and to control the rate of polymerization and melting. Other techniques such as determination of c(sat) and the more conventional methods for measuring polymerization progress curves, such as light scattering, will be used to supplement the DCI technique.